EARLY STEPS IN DROSOPHILA SEX DETERMINATION

这项研究的目标是从分子水平上理解早期的 以果蝇性别决定途径的步骤为例 一种实验上容易控制的发育开关。关注的焦点是 调控基因性致死，它在短时间内起作用 由性别特定的、可供选择的基因调控的基因层次 核糖核酸拼接。SXL生成的转录被拼接成 雌性为功能性形式，而雄性为非功能性形式。SXL 是在最初的途径信号之后第一个被发现的基因， X染色体与常染色体的比率。SXL的早期反应是 以观察到的一组女性特有的转录本为特征 在早期胚胎发育中是暂时的；这些不同于 后来的转录本受剪接调控。调控基因 控制这一早期步骤将在 为了阐明机制，能够区分 一条和两条X染色体。方法将是设计出基因 筛选现有信号元件突变的抑制子，以及 早期筛选与SXL增强子结合的蛋白质 推动者。调控蛋白及其与DNA的相互作用 将会被检查。 果蝇与人类发育的相关性一直很好 通过描述同源异型盒基因及其 在哺乳动物胚胎中的表达模式。A的定义 遗传开关，如果蝇的性别决定，也可能是 预计将为人类调节机制提供一个模型 发展。

The goal of this research is a molecular understanding of the early steps of the Drosophila sex determination pathway as an example of an experimentally tractable developmental switch. The focus is the regulatory gene Sex-lethal, which functions at the start of a short hierarchy of genes that are regulated by sex-specific, alternative RNA splicing. Sxl produces transcripts that are spliced into a functional form in females but a non-functional form in males. Sxl is the first identified gene after the initial pathway signal, the ratio of X chromosomes to autosomes. Sxl's early response is characterized by a set of female-specific transcripts observed transiently in early embryogenesis; these are distinct from the later transcripts regulated by splicing. Regulatory genes that control this early step will be identified and characterized in order to elucidate the mechanism capable of distinguishing between one and two X chromosomes. The approach will be to devise genetic screens for suppressors of existing signal element mutations, and to screen for proteins that bind enhancers of the Sxl early promoter. Interactions between regulatory proteins and with DNA will be examined. The relevance of Drosophila to human development has been well established with the description of homeobox genes and their pattern of expression in mammalian embryos. Definition of a genetic switch such as Drosophila sex determination may likewise be expected to provide a model for human regulatory mechanisms in development.